AID hits the jackpot when missing the target.
Abstract Activation induced deaminase is the single B cell specific factor mediating class switch recombination and somatic hypermutation. Numerous studies have shown that AID preferentially targets Ig substrates and also attacks non-Ig substrates to create DNA damage that contributes to lymphomagenesis. AID targeting to Ig loci is linked to transcription but the mechanism governing this process has been obscure. Here we discuss research that illustrates the connection between AID targeting to DNA substrates and transcription processes to reveal rules governing the specificity of AID attack. These observations are...
Source: Current Opinion in Immunology - February 1, 2016 Category: Allergy & Immunology Authors: Kenter AL, Kumar S, Wuerffel R, Grigera F Tags: Curr Opin Immunol Source Type: research

Dendritic cell function and antigen presentation in malaria.
Abstract Due to the diverse roles T cells play in protection against malaria as well as pathogenesis it is critical to know which cells present antigen and the nature of the antigens they present. During pre-erythrocytic stages of infection, cutting-edge imaging studies have shown how Plasmodium antigens are presented during both the priming and effector phases of the protective CD8+ T cell response. During blood stages, pathology is in part due to the loss of DC function and the action of pathogenic T cells in the brain. Recently endothelial cells presenting malaria antigen to cognate T cells have emerged as crit...
Source: Current Opinion in Immunology - February 1, 2016 Category: Allergy & Immunology Authors: Cockburn IA, Zavala F Tags: Curr Opin Immunol Source Type: research

Adoptive cell therapy: a highly successful individualized therapy for melanoma with great potential for other malignancies.
Abstract Adoptive cell therapy (ACT) by infusion of autologous or redirected tumor-specific T-cells has had a major impact on the treatment of several metastasized malignancies that were until now hardly treatable. Recent findings provide a more profound knowledge on the underlying mechanisms of success and allow the optimization of the ACT protocol with respect to (1) the treatment related side-effects, (2) the quality and specificity of infused T-cells, and (3) the immunosuppressive phenotype of the tumor environment. In this review, the results and insights in the success of ACT as well as the possibilities to ...
Source: Current Opinion in Immunology - January 29, 2016 Category: Allergy & Immunology Authors: Verdegaal EM Tags: Curr Opin Immunol Source Type: research

The role of microbiota in cancer therapy.
Abstract The relationship between the host and the commensal microbiota regulates physiological functions including inflammation and immunity and it has been scrutinized in the context of cancer. While viruses and bacterial species have been implicated in oncogenesis, commensal microbes also have a beneficial role in the fight against cancer. Therapy efficacy, including adoptive T cell transfer, alkylating agents and immune checkpoint blockers, relies on immunity that receives its education from the gut microbiota. In cancer therapy with immunostimulating oligonucleotides and platinum salts, the microbiota also mo...
Source: Current Opinion in Immunology - January 25, 2016 Category: Allergy & Immunology Authors: Perez-Chanona E, Trinchieri G Tags: Curr Opin Immunol Source Type: research

Development of invariant natural killer T cells.
Abstract Invariant natural killer T (iNKT) cells develop into functionally distinct subsets. Each subset expresses a unique combination of transcription factors that regulate cytokine gene transcription upon activation. The tissue distribution and localization within tissues also varies between subsets. Importantly, the relative abundance of the various subsets is directly responsible for altering several immunological parameters, which subsequently affect the immune response. Here, I review recent advances in our understanding of the molecular regulation of iNKT cell subset development. PMID: 26802287 [PubMe...
Source: Current Opinion in Immunology - January 20, 2016 Category: Allergy & Immunology Authors: Gapin L Tags: Curr Opin Immunol Source Type: research

Cancer immunoprevention.
Abstract Cancer immunotherapy is now a reality. The results are phenomenal but the cost is outrageous. Even if the cost eventually comes down and immunotherapy becomes more broadly available, using the knowledge derived from immunotherapy to apply to immunoprevention would be a good strategy. The most likely approach to cancer immunoprevention is cancer vaccines. To date, cancer vaccines have been tested mostly in the setting of advanced disease. Numerous immunosuppressive mechanisms have been identified in the tumor microenvironment as well as systemically that compromise the ability of cancer patients to respond...
Source: Current Opinion in Immunology - January 19, 2016 Category: Allergy & Immunology Authors: Finn OJ, Beatty PL Tags: Curr Opin Immunol Source Type: research

Regulation of germinal center responses, memory B cells and plasma cell formation-an update.
Abstract Progress in understanding humoral immunity has been accelerated by the powerful experimental approaches of genetics, genomics and imaging. Excellent reviews of these advances appeared in 2015 in celebration of the 50th anniversary of the discovery of B cell and T cell lineages in the chicken. Here we provide a contemporary model of B cell differentiation, highlighting recent publications illuminating germinal center (GC), memory B cell and antibody-secreting plasma cell biology. The important contributions of CD4T cells to antibody responses have been thoroughly reviewed elsewhere. PMID: 26799208 [Pu...
Source: Current Opinion in Immunology - January 19, 2016 Category: Allergy & Immunology Authors: Corcoran LM, Tarlinton DM Tags: Curr Opin Immunol Source Type: research

The urgent need to recover MHC class I in cancers for effective immunotherapy.
Abstract Immune escape strategies aimed to avoid T-cell recognition, including the loss of tumor MHC class I expression, are commonly found in malignant cells. Tumor immune escape has proven to have a negative effect on the clinical outcome of cancer immunotherapy, including treatment with antibodies blocking immune checkpoint molecules. Hence, there is an urgent need to develop novel approaches to overcome tumor immune evasion. MHC class I antigen presentation is often affected in human cancers and the capacity to induce upregulation of MHC class I cell surface expression is a critical step in the induction of tu...
Source: Current Opinion in Immunology - January 18, 2016 Category: Allergy & Immunology Authors: Garrido F, Aptsiauri N, Doorduijn EM, Garcia Lora AM, van Hall T Tags: Curr Opin Immunol Source Type: research

Treg stability: to be or not to be.
Abstract Regulatory T cell (Treg) stability has been primarily determined by the maintained expression of the transcription factor Forkhead box P3 (Foxp3). However, Tregs can exhibit instability while maintaining Foxp3 expression, requiring a re-examination of what defines Treg stability. Recent work suggests that the establishment and stability of Tregs is mediated by a number of mechanisms besides Foxp3 expression, such as epigenetic modifications, Foxo1/3a localization, expression of Eos and signaling via Neuropilin-1. Additional studies may help to define approaches that can undermine Treg stability in cancer ...
Source: Current Opinion in Immunology - January 14, 2016 Category: Allergy & Immunology Authors: Overacre AE, Vignali DA Tags: Curr Opin Immunol Source Type: research

Melanoma: the intersection of molecular targeted therapy and immune checkpoint inhibition.
Abstract Melanoma is at the forefront of development of systemic therapeutics with both molecular targeted therapies and immune checkpoint inhibitors as cornerstones of treatment. Although responses to molecularly targeted therapy is largely from blockade of oncogenic pathways, evidence is emerging of the immunomodulatory effects from BRAF inhibition. Additionally programmed-death-1 (PD-1) inhibitors have revolutionized the treatment of melanoma and are set to pave future improvements in other solid tumors. Combinations of PD-1 inhibitors with novel immune checkpoints or with molecularly targeted therapies are und...
Source: Current Opinion in Immunology - January 5, 2016 Category: Allergy & Immunology Authors: Lau PK, Ascierto PA, McArthur G Tags: Curr Opin Immunol Source Type: research

Host genetics of severe influenza: from mouse Mx1 to human IRF7.
Abstract Influenza viruses cause mild to moderate respiratory illness in most people, and only rarely devastating or fatal infections. The virulence factors encoded by viral genes can explain seasonal or geographic differences at the population level but are unlikely to account for inter-individual clinical variability. Inherited or acquired immunodeficiencies may thus underlie severe cases of influenza. The crucial role of host genes was first demonstrated by forward genetics in inbred mice, with the identification of interferon (IFN)-α/β-inducible Mx1 as a canonical influenza susceptibility gene. Reve...
Source: Current Opinion in Immunology - January 4, 2016 Category: Allergy & Immunology Authors: Ciancanelli MJ, Abel L, Zhang SY, Casanova JL Tags: Curr Opin Immunol Source Type: research

Innate myeloid cells under the control of adaptive immunity: the example of mast cells and basophils.
n M Abstract Mast cells and basophils are mostly known as the initiators of IgE-dependent allergic reactions. They, however, contribute to innate immunity against pathogens and venoms. Like other myeloid cells, they also express receptors for the Fc portion of IgG antibodies. These include activating receptors and inhibitory receptors. Because IgG antibodies are produced in exceedingly higher amounts than IgE antibodies, IgG receptors are co-engaged with IgE receptors under physiological conditions. Mast cells and basophils are examples of the many innate myeloid cells whose effector functions are used and finely ...
Source: Current Opinion in Immunology - December 30, 2015 Category: Allergy & Immunology Authors: Daëron M Tags: Curr Opin Immunol Source Type: research

Red alert: labile heme is an alarmin.
In conclusion, we propose that labile heme is an alarmin. PMID: 26741528 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - December 29, 2015 Category: Allergy & Immunology Authors: Soares MP, Bozza MT Tags: Curr Opin Immunol Source Type: research

Innate lymphoid cells: parallel checkpoints and coordinate interactions with T cells.
Abstract Protection of epithelial and mucosal surfaces is required for survival. The recent discovery of a diverse array of innate lymphoid cells that lie immediately beneath these surfaces has unexpectedly uncovered an entire defense system distinct from the adaptive system essential to protect these barriers. This multilayered design provides a robust system through coupling of two highly complementary networks to ensure immune protection. Here, we discuss the similarities in the hardwiring and diversification of innate lymphoid cells and T cells during mammalian immune responses. PMID: 26736074 [PubMed - a...
Source: Current Opinion in Immunology - December 28, 2015 Category: Allergy & Immunology Authors: Huntington ND, Carpentier S, Vivier E, Belz GT Tags: Curr Opin Immunol Source Type: research

Editorial overview: Innate immunity.
PMID: 26739338 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - December 28, 2015 Category: Allergy & Immunology Authors: Vivier E, Medzhitov R Tags: Curr Opin Immunol Source Type: research

Chemotherapy and immunotherapy: mapping the road ahead.
Abstract Cancer immunotherapy, and in particular checkpoint blockade, is now standard clinical care for a growing number of cancers. Cytotoxic drugs have been the primary weapon against cancer for a long time and have typically been understood because of their capacity to directly kill tumour cells. It is now clear that these drugs are potential partners for checkpoint blockade and different drugs can influence the immune response to cancer through a wide variety of mechanisms. Some of these relate to immunogenic cell death, whilst others relate to changes in antigen-presentation, tumour cell targeting, or depleti...
Source: Current Opinion in Immunology - December 24, 2015 Category: Allergy & Immunology Authors: Cook AM, Lesterhuis WJ, Nowak AK, Lake RA Tags: Curr Opin Immunol Source Type: research

Mutanome directed cancer immunotherapy.
Sahin U Abstract Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic the...
Source: Current Opinion in Immunology - December 21, 2015 Category: Allergy & Immunology Authors: Vormehr M, Diken M, Boegel S, Kreiter S, Türeci Ö, Sahin U Tags: Curr Opin Immunol Source Type: research

Differentiation of human innate lymphoid cells (ILCs).
Abstract During the last years, a high complexity in innate lymphoid lineages now collectively referred to as innate lymphoid cells (ILCs) has been revealed. ILCs can be grouped according to their effector functions and transcriptional requirements into three main groups, termed group 1, 2 and 3 ILCs. The differentiation of ILC lineages from hematopoietic precursors and the molecular switches guiding their developmental fate have started to be characterized both in mice and humans. In this review, we discuss the origin, differentiation stages and plasticity of human ILC subsets as well as the signals that drive IL...
Source: Current Opinion in Immunology - December 17, 2015 Category: Allergy & Immunology Authors: Juelke K, Romagnani C Tags: Curr Opin Immunol Source Type: research

Cancer immune contexture and immunotherapy.
an WH Abstract The immune contexture that characterizes the density, the location, the organization and the functional orientation of tumor-infiltrating immune cells in cancers has a clinical impact on patient's outcome. It is, in great part, shaped by the malignant cells, as in a given cancer type, tumors presenting different oncogenic processes have different immune contextures. Moreover, the immune contexture in metastatic sites reflects that of the corresponding primary tumors. Finally, the components forming the immune contexture represent targets and markers of efficient anti-cancer immunotherapies. PMI...
Source: Current Opinion in Immunology - December 17, 2015 Category: Allergy & Immunology Authors: Becht E, Giraldo NA, Dieu-Nosjean MC, Sautès-Fridman C, Fridman WH Tags: Curr Opin Immunol Source Type: research

Phenotype and functions of conventional and non-conventional NK cells.
Abstract Here we focus on the phenotypic and functional diversity of NK cells. We give an overview of the phenotype and developmental pathways of conventional and tissue-resident NK cells. We also discuss the potential complementary functions of conventional NK cells and tissue-resident NK cells in a variety of tissues. PMID: 26706497 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - December 16, 2015 Category: Allergy & Immunology Authors: Erick TK, Brossay L Tags: Curr Opin Immunol Source Type: research

Immunosurveillance and immunotherapy of tumors by innate immune cells.
Abstract Increasing evidence supports a role for innate immune effector cells in tumor surveillance. Natural killer (NK) cells and myeloid cells represent the two main subsets of innate immune cells possessing efficient but quite different tumor suppressive abilities. Here, we describe the germline-encoded NK cell receptors that play a role in suppressing tumor development and describe briefly the cellular pathways leading to the upregulation of their ligands in tumor cells. We also describe mechanisms underlying the elimination of tumor cells by macrophages and a recently characterized mechanism dedicated to sens...
Source: Current Opinion in Immunology - December 11, 2015 Category: Allergy & Immunology Authors: Iannello A, Thompson TW, Ardolino M, Marcus A, Raulet DH Tags: Curr Opin Immunol Source Type: research

Beyond the grave: When is cell death critical for immunity to infection?
Abstract Immune cell death is often observed in response to infection. There are three potential beneficial outcomes after host cell death: (1) the removal of an intracellular niche for microbes, (2) direct microbicidal activity of released components and (3) the propagation of an inflammatory response. Recent findings suggest that three forms of non-apoptotic regulated cell death, pyroptosis, necroptosis and NETosis, can impact on immunity to bacterial infection. However, it is challenging to design experiments that unequivocally prove the advantageous effects of regulated cell death on immunity. Recent advances ...
Source: Current Opinion in Immunology - December 9, 2015 Category: Allergy & Immunology Authors: Stephenson HN, Herzig A, Zychlinsky A Tags: Curr Opin Immunol Source Type: research

SLAM family receptors in normal immunity and immune pathologies.
Abstract The signaling lymphocytic activation molecule (SLAM) family is a group of six receptors restricted to hematopoietic cells. Most of these receptors are self-ligands, and thus are triggered in the context of interactions between hematopoietic cells. By way of their cytoplasmic domain, SLAM-related receptors associate with the SLAM-associated protein (SAP) family of adaptors, which control the signals and functions of SLAM family receptors. Recent findings have provided new insights into the key roles of SLAM family receptors in normal immunity, their involvement in human diseases and their usefulness as dru...
Source: Current Opinion in Immunology - December 2, 2015 Category: Allergy & Immunology Authors: Wu N, Veillette A Tags: Curr Opin Immunol Source Type: research

PTX3, a humoral pattern recognition molecule at the interface between microbe and matrix recognition.
Abstract Innate immunity consists of a cellular and a humoral arm. PTX3 is a fluid patter recognition molecule (PRM) with antibody-like properties. Gene targeted mice and genetic associations in humans suggest that PTX3 plays a non-redundant role in resistance against selected pathogens (e.g. Aspergillus fumigatus, Pseudomonas aeruginosa, uropathogenic Escherichia coli) and in the regulation of inflammation. PTX3 acts as an extrinsic oncosuppressor by taming complement elicited tumor-promoting inflammation. Recent results indicate that, by interacting with provisional matrix components, PTX3 contributes to the orc...
Source: Current Opinion in Immunology - November 30, 2015 Category: Allergy & Immunology Authors: Garlanda C, Jaillon S, Doni A, Bottazzi B, Mantovani A Tags: Curr Opin Immunol Source Type: research

Immune suppressive mechanisms in the tumor microenvironment.
Abstract Effective immunotherapy, whether by checkpoint blockade or adoptive cell therapy, is limited in most patients by a key barrier: the immunosuppressive tumor microenvironment. Suppression of tumor-specific T cells is orchestrated by the activity of a variety of stromal myeloid and lymphoid cells. These often display inducible suppressive mechanisms that are triggered by the same anti-tumor inflammatory response that the immunotherapy intends to create. Therefore, a more comprehensive understanding of how the immunosuppressive milieu develops and persists is critical in order to harness the full power of imm...
Source: Current Opinion in Immunology - November 20, 2015 Category: Allergy & Immunology Authors: Munn DH, Bronte V Tags: Curr Opin Immunol Source Type: research

BCR and co-receptor crosstalk facilitate the positive selection of self-reactive transitional B cells.
Abstract The establishment of a diverse B cell repertoire requires fine-tuning of antigen receptor selection during development in order to permit sufficient diversity while reducing the potential for autoimmunity. In this review, we highlight recent studies demonstrating the central role of the B cell antigen receptor (BCR), in coordination with other key pro-survival signals mediated by CD40, BAFF-R, TACI and/or TLRs, in regulating both negative and positive selection of autoreactive B cells. In particular, we show how altered antigen or co-stimulatory signaling can facilitate positive selection of transitional ...
Source: Current Opinion in Immunology - November 19, 2015 Category: Allergy & Immunology Authors: Metzler G, Kolhatkar NS, Rawlings DJ Tags: Curr Opin Immunol Source Type: research

Metabolic adaptation of tissues to stress releases metabolites influencing innate immunity.
Abstract Recent developments have demonstrated that metabolic rewiring imposed by adaptation of tissues to stress leads to the release of various metabolites which directly or indirectly impact innate immune responses and inflammation. Some metabolites can behave as second messengers and leave local cues in tissues. Immune cells which infiltrate stressed tissues reorient their metabolism to cope with these microenvironmental cues while preserving their effector functions in tissues. PMID: 26605965 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - November 19, 2015 Category: Allergy & Immunology Authors: Naquet P, Giessner C, Galland F Tags: Curr Opin Immunol Source Type: research

Mechanisms of restriction of viral neuroinvasion at the blood-brain barrier.
Abstract The blood-brain barrier (BBB) consists of highly specialized cells including brain microvascular endothelial cells, astrocytes, microglia, pericytes, and neurons, which act in concert to restrict the entry of pathogens, immune cells, and soluble molecules into the central nervous system (CNS). If pathogens manage to cross the BBB and establish infection within the CNS, the BBB can open in a regulated manner to allow leukocyte transmigration into the CNS so that microbes, infected cells, and debris can be cleared. This review highlights how different inflammatory cytokines or signaling pathways disrupt or ...
Source: Current Opinion in Immunology - November 16, 2015 Category: Allergy & Immunology Authors: Miner JJ, Diamond MS Tags: Curr Opin Immunol Source Type: research

Localized signals that regulate transendothelial migration.
Abstract Transendothelial migration (TEM) of leukocytes is the step in leukocyte emigration in which the leukocyte actually leaves the blood vessel to carry out its role in the inflammatory response. It is therefore, arguably the most critical step in emigration. This review focuses on two of the many aspects of this process that have seen important recent developments. The adhesion molecules, PECAM (CD31) and CD99 that regulate two major steps in TEM, do so by regulating specific signals. PECAM initiates the signaling pathway responsible for the calcium flux that is required for TEM. Calcium enters through the ca...
Source: Current Opinion in Immunology - November 13, 2015 Category: Allergy & Immunology Authors: Muller WA Tags: Curr Opin Immunol Source Type: research

Sensing Gram-negative bacteria: a phylogenetic perspective.
Abstract Gram-negative bacteria represent a major group of pathogens that infect all eukaryotes from plants to mammals. Gram-negative microbe-associated molecular patterns include lipopolysaccharides and peptidoglycans, major immunostimulatory determinants across phyla. Recent advances have furthered our understanding of Gram-negative detection beyond the well-defined pattern recognition receptors such as TLR4. A B-type lectin receptor for LPS and Lysine-motif containing receptors for peptidoglycans were recently added to the plant arsenal. Caspases join the ranks of mammalian cytosolic immune detectors by binding...
Source: Current Opinion in Immunology - November 10, 2015 Category: Allergy & Immunology Authors: Neyen C, Lemaitre B Tags: Curr Opin Immunol Source Type: research

RIG-I-like receptors and autoimmune diseases.
Abstract Type I interferon (IFN) plays an essential role in antiviral innate immune responses and also in adaptive immune responses. Defects in the production of IFN markedly increase susceptibility to viral invasion and attenuate the acquired immunity. Recently an increased expression of type I IFN, also termed IFN signature, has been reported in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS). The evidence clearly shows that the initiation and termination of IFN production should be tightly controlled. RIG-I-like receptors (RLRs) are viral ...
Source: Current Opinion in Immunology - October 27, 2015 Category: Allergy & Immunology Authors: Kato H, Fujita T Tags: Curr Opin Immunol Source Type: research

Local and long-range activation of innate immunity by infection and damage in C. elegans.
Abstract The nematode worm Caenorhabditis elegans lends itself naturally to investigation of innate immunity, from the scale of molecules to the whole animal. Numerous studies have begun to reveal the complex interplay of signalling mechanisms that underlie host defence in C. elegans. We discuss here research that illustrates the connection between cell and tissue-level homeostatic mechanisms and the activation of innate immune signalling pathways. These are woven together to provide a comprehensive organismal protection against perceived threats. PMID: 26517153 [PubMed - as supplied by publisher] (Source: Cu...
Source: Current Opinion in Immunology - October 27, 2015 Category: Allergy & Immunology Authors: Ewbank JJ, Pujol N Tags: Curr Opin Immunol Source Type: research

Editorial overview: Autoimmunity.
PMID: 26510378 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - October 25, 2015 Category: Allergy & Immunology Authors: Anderson MS, Mackay F Tags: Curr Opin Immunol Source Type: research

Immuno-ecology: how the microbiome regulates tolerance and autoimmunity.
Abstract The trillions of microorganisms populating the mammalian mucosal surfaces (i.e. the microbiome) participate in the development and function of the host immune system that acts to balance clearance of pathogens with tolerance of beneficial commensals. Recent advances in mucosal immunology and culture-independent sequencing of microbial communities provide support for the hypothesis that the alterations in commensal microbiota alter the host immune response and can enhance risk for autoimmune disease in distant organs. Further explorations of the host-microbiota relationship will improve our understanding o...
Source: Current Opinion in Immunology - October 10, 2015 Category: Allergy & Immunology Authors: Paun A, Danska JS Tags: Curr Opin Immunol Source Type: research

Identifying genetic determinants of autoimmunity and immune dysregulation.
Abstract Common autoimmune diseases are relatively heterogeneous with both genetic and environmental factors influencing disease susceptibility and progression. As the populations in developed countries age, these chronic diseases will become an increasing burden in human suffering and health care costs. By contrast, rare immune diseases that are severe and develop early in childhood are frequently monogenic and fully penetrant, often with a Mendelian inheritance pattern. Although these may be incompatible with survival or cured by hematopoietic stem cell transplantation, we will argue that they constitute a rich ...
Source: Current Opinion in Immunology - October 1, 2015 Category: Allergy & Immunology Authors: Lucas CL, Lenardo MJ Tags: Curr Opin Immunol Source Type: research

Targeting Treg signaling for the treatment of autoimmune diseases.
Abstract Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Treg lineage commitment and functional stability are influenced by selected extracellular signals from the local environment, shaped by distinctive intracellular signaling network, and secured by their unique epigenetic profile. Recent advances in our understanding of the complex processes of Treg lineage differentiation, maintenance, and function has paved the way for developing strategies to manipulate these important cells for therapeutic benefit in many diseases. In this review, we will summarize recent advances in our un...
Source: Current Opinion in Immunology - September 29, 2015 Category: Allergy & Immunology Authors: Spence A, Klementowicz JE, Bluestone JA, Tang Q Tags: Curr Opin Immunol Source Type: research

Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity.
Abstract T follicular helper (Tfh) cells are crucial to induce protective extrafollicular and germinal center antibody responses against protein antigens. Over the last decade, control of Tfh cell numbers has emerged as an important regulatory checkpoint which, when perturbed, may lead to production of autoantibodies. Recent progress in understanding how Tfh cells are kept limiting has revealed an important role for posttranscriptional control of gene expression mediated by microRNAs such as miR-17∼92, miR-155 and miR-146a, and the RNA-binding proteins Roquin and Regnase. Additionally, T cell microRNAs dysregu...
Source: Current Opinion in Immunology - September 29, 2015 Category: Allergy & Immunology Authors: Jiang SH, Shen N, Vinuesa CG Tags: Curr Opin Immunol Source Type: research

Genetics of allergy and allergic sensitization: common variants, rare mutations.
er JD Abstract Our understanding of the specific genetic lesions in allergy has improved in recent years due to identification of common risk variants from genome-wide association studies (GWAS) and studies of rare, monogenic diseases. Large-scale GWAS have identified novel susceptibility loci and provided information about shared genetics between allergy, related phenotypes and autoimmunity. Studies of monogenic diseases have elucidated critical cellular pathways and protein functions responsible for allergy. These complementary approaches imply genetic mechanisms involved in Th2 immunity, T-cell differentiation,...
Source: Current Opinion in Immunology - September 16, 2015 Category: Allergy & Immunology Authors: Bønnelykke K, Sparks R, Waage J, Milner JD Tags: Curr Opin Immunol Source Type: research

Editorial overview: Host pathogens: New paradigms and tools to decipher and deconstruct the host-pathogen interaction.
PMID: 26359003 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - September 7, 2015 Category: Allergy & Immunology Authors: Silvestri G, Barry PA Tags: Curr Opin Immunol Source Type: research

Editorial overview: Allergy and hypersensitivity: New developments in allergy and type 2 immunity: never a dull moment.
PMID: 26337485 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 31, 2015 Category: Allergy & Immunology Authors: Vercelli D, Galli SJ Tags: Curr Opin Immunol Source Type: research

Effector T cell differentiation: are master regulators of effector T cells still the masters?
Abstract Effector CD4 T cell lineages have been implicated as potent inducers of autoimmune diseases. Tbet, Gata3 and Rorgt are master transcriptional regulators of Th1, Th2 and Th17 lineages respectively and promote the distinct expression of signature cytokines. Significant progress has been made in understanding the transcriptional network that drives CD4 T cell differentiation, revealing novel points of regulation mediated by transcription factors, cell surface receptors, cytokines and chemokines. Epigenetic modifications and metabolic mediators define the transcriptional landscape in which master transcriptio...
Source: Current Opinion in Immunology - August 26, 2015 Category: Allergy & Immunology Authors: Wang C, Collins M, Kuchroo VK Tags: Curr Opin Immunol Source Type: research

IgE receptor signaling in food allergy pathogenesis.
Abstract The pathogenesis of food allergy remains poorly understood. Recent advances in the use of murine models have led to discoveries that mast cells and IgE receptor signaling not only drive immediate hypersensitivity reactions but also exert an immunoregulatory function, promoting the development of allergic sensitivity to foods. We review the evidence that IgE, IgE receptors, key signaling kinases and mast cells impair oral tolerance to ingested foods, preventing the induction of regulatory T cells (Treg) and promoting the acquisition of pro-allergic T helper (Th) 2 responses. We discuss innovative strategie...
Source: Current Opinion in Immunology - August 18, 2015 Category: Allergy & Immunology Authors: Oettgen HC, Burton OT Tags: Curr Opin Immunol Source Type: research

Editorial overview: Special section: Immunological engineering.
PMID: 26275317 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 11, 2015 Category: Allergy & Immunology Authors: Irvine DJ, Ploegh H Tags: Curr Opin Immunol Source Type: research

Editorial overview: Vaccines: Vaccines for cancer and infectious diseases.
PMID: 26275318 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 11, 2015 Category: Allergy & Immunology Authors: Mascola J, Ahmed R Tags: Curr Opin Immunol Source Type: research

Novel monogenic diseases causing human autoimmunity.
Abstract Fuelled by the on-going sequencing revolution, the last two years have seen a number of exciting discoveries relating to monogenic disorders predisposing to autoimmunity that provide new insights into the function of the human immune system. Here we discuss a selection of these diseases due to mutations in PRKCD, CTLA4, STAT3, IFIH1, TMEM173 and COPA. PMID: 26262888 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - August 8, 2015 Category: Allergy & Immunology Authors: Melki I, Crow YJ Tags: Curr Opin Immunol Source Type: research

MicroRNA regulation of allergic inflammation and asthma.
Abstract Allergic diseases are prevalent and clinically heterogeneous, and are the pathologic consequence of inappropriate or exaggerated type 2 immune responses. In this review, we explore the role of microRNAs (miRNAs) in regulating allergic inflammation. We discuss how miRNAs, acting through target genes to modulate gene expression networks, impact multiple facets of immune cell function critical for type 2 immune responses including cell survival, proliferation, differentiation, and effector functions. Human and mouse studies indicate that miRNAs are significant regulators of allergic immune responses. Finally...
Source: Current Opinion in Immunology - August 4, 2015 Category: Allergy & Immunology Authors: Pua HH, Ansel KM Tags: Curr Opin Immunol Source Type: research

Immunology and evolvement of the adenovirus prime, MVA boost Ebola virus vaccine.
Abstract The 2014 Ebola virus outbreak caused an order of magnitude more deaths in a single outbreak than all previous known outbreaks combined, affecting both local and international public health, and threatening the security and economic stability of the countries in West Africa directly confronting the outbreak. The severity of the epidemic lead to a global response to assist with patient care, outbreak control, and deployment of vaccines. The latter was possible due to the long history of basic and clinical research aimed at identifying a safe and effective vaccine to protect against Ebola virus infection. Th...
Source: Current Opinion in Immunology - August 3, 2015 Category: Allergy & Immunology Authors: Zhou Y, Sullivan NJ Tags: Curr Opin Immunol Source Type: research

Hepatitis C virus: why do we need a vaccine to prevent a curable persistent infection?
The objective of HCV vaccination is not to induce sterilizing immunity, but instead to prevent persistent infection. One vaccine that incorporates only non-structural HCV proteins is now in phase I/II efficacy trials to test the novel concept that T cell priming alone is sufficient for protection. Evidence also suggests that antibodies contribute to infection resolution. Vaccines comprised of recombinant envelope glycoproteins targeted by neutralizing antibodies have been assessed in humans for immunogenicity. Here, we discuss current concepts in protective immunity and divergent approaches to vaccination against a highly ...
Source: Current Opinion in Immunology - August 1, 2015 Category: Allergy & Immunology Authors: Walker CM, Grakoui A Tags: Curr Opin Immunol Source Type: research

Microbiome influences on allergy in mice and humans.
Abstract The microbiota plays a pivotal role in the development and calibration of host immunity. Over many millennia, finely balanced interactions between the microbiota and host tissue compartments have evolved, imparting metabolic advantages and protection against pathogens, while restricting deleterious immune responses against innocuous antigens. Perturbations in host-microbiota crosstalk at critical developmental windows in early life may underlie allergy and chronic inflammation. Although the microbiota's of the gut and skin have been extensively characterized, the lung microbiota has also, in recent years,...
Source: Current Opinion in Immunology - July 25, 2015 Category: Allergy & Immunology Authors: Marsland BJ, Salami O Tags: Curr Opin Immunol Source Type: research

Synthetic biology approaches to engineer T cells.
Abstract There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order ...
Source: Current Opinion in Immunology - July 23, 2015 Category: Allergy & Immunology Authors: Wu CY, Rupp LJ, Roybal KT, Lim WA Tags: Curr Opin Immunol Source Type: research